Gene Therapy: SCHN leaders in Advanced Therapeutics

Luminesce Alliance partners are Australia’s leaders in Paediatric Gene Therapy

Luminesce Alliance partners are national leaders in diagnostic, data and disease modelling research, with the knowledge and expertise that will be required to develop, evaluate and deliver novel disruptive therapies for rare disorders in children.

Read more on how you can get in touch with us today for advice and assistance on paediatric gene therapy.

 

Economic Evaluation of newborn screening for severe combined immunodeficiency and SMA

Luminesce Alliance funded the recently published report on the Economic Evaluation of newborn screening for severe combined immunodeficiency and spinal muscular atrophy.

The aim of the economic evaluation was to investigate the costs and outcomes associated with the introduction of population based newborn screening (NBS) for Severe Combined Immunodeficiency (SCID) and spinal muscular atrophy (SMA) by generating measures of cost-effectiveness and budget impact. The economic question was whether a state-wide SMA and SCID NBS programme with presymptomatic treatment for these diseases is more cost-effective than clinical diagnosis and late initiation of treatment.

 

From an economic evaluation perspective, the findings indicate that the combined introduction of NBS for SCID and SMA would be considered cost-effective and cost-saving from a government perspective if combined with stem cell transplant for SCID and gene therapy for SMA.  The main limitation of this study is a lack of  long-term clinical data on novel treatments, such as gene therapy and nusinersen, to treat SMA. Comprehensive longitudinal follow-up data from the NSW/ACT screening pilot for these conditions will provide a better understanding of the impact of NBS on newly identified cases of SMA and SCID and inform improvements in NBS programmes and clinical care.

 

The report was prepared by the National Perinatal Epidemiology and Statistics Unit (NPESU) a unit within the Centre for Big Data Research in Health and the School of Women’s and Children’s Health of the University of New South Wales, Sydney (UNSW). The study was led by Prof Georgina M Chambers in collaboration with Dr Sophy TF Shih, Assoc Prof Michelle A Farrar,  Dr Veronica Wiley, Dr Melanie Wong, and Elena Keller.

 

Innovation in Paediatric Precision Medicine Seed Funding Outcomes

The Luminesce Alliance Innovation in Paediatric Precision Medicine Seed Funding Round has been a tremendous success. Fifty nine applications were received with a total funding request of just under $11 million. This was more than anticipated. With a total funding pool of just $1 million it was not possible to fund all projects. The successful seed funding applications were:

A self-amplifying theranostic for treatment of neuroblastoma, Professor Phillip Hogg, University of Sydney

This study aims to evaluate the therapeutic efficacy of 177Lu-CDI in unprimed or cyclophosphamide-primed murine neuroblastoma tumours. It is hypothesise that 177Lu-CDI will bind to dying/dead neuroblastoma tumour cells and deliver therapeutic radiation to viable, potentially more resistant tumour cells adjacent to the dying /dead cells, and in combination with sensitising chemotherapy will generate a self-amplifying cascade of neuroblastoma tumour cell kill.

 

Curing genetic metabolic liver disease by precise genomic and epigenomic editing, Professor Ian Alexander, Children’s Medical Research Institute

While individually rare, genetic metabolic liver diseases are collectively common, difficult to treat and carry high morbidity and mortality. This study hypothesise that precise genetic and epigenetic editing at the human Ornithine transcarbamylase deficiency (OTC) locus can be used to restore physiological OTC expression in male and female patient-derived primary human hepatocytes in vivo at clinically relevant efficiencies. One of its aims is to optimize the efficient delivery of genetic and epigenetic editing reagents to patient-derived OTC-deficient primary human hepatocytes in vivo using elite AAV capsid technology (AAV-LB12) in combination with lipid nanoparticle (LNP) technology.

 

Translating disease severity biomarkers into the clinic for Rett syndrome, Professor Wendy Gold, University of Sydney

Rett syndrome is a rare severe neurodevelopmental disorder caused by variants in the Methyl-CpG-binding protein 2 (MECP2) gene. It is the second most common form of intellectual impairment in females. One of the aims of the study is to determine whether serum levels of FGF21 and GDF15 are prognostic biomarkers of disease stage and severity in girls with Rett syndrome.

 

Precision medicine addressing a novel disease pathway to preserve sight in the retinal dystrophies, Professor Robyn Jamieson,  Children’s Medical Research Institute

Inherited Retinal Diseases (IRDs) affect approximately 1:1000 people or leads to an inexorable degeneration to blindness. There is marked genetic heterogeneity hampering individual gene therapeutic efforts. This project aims to develop a novel therapeutic approach towards a disease pathway we have recently identified, that will be applicable to the broad group of IRDs, thus able to benefit a large proportion of patients.

 

LA Centre for RNA Diagnostics: A pipeline of accredited RNA Diagnostics to extend diagnostic yield of rare disorders by 25 % in 5 years, Professor Sandra Cooper, Sydney Children’s Hospitals Network

Variants of Uncertain Significance (VUS) leaves families and clinicians with no actionable answer and health systems with no diagnostic return on their investment into genetic sequencing. This health implementation project will establish a centre for RNA Diagnostics that will provide an accredited RNA diagnostic service with 95% diagnostic return (ie 95% variant re-classification). It will aim to resolve pathogenicity of splicing variant VUS for 60 families with rare monogenic disorders or germline cancer.

 

The reviewers commented on the diversity received and the high calibre of the applications. It was very encouraging to see the breath of paediatric precision medicine research emerging from the Luminesce Alliance partners.